title: Genetic predisposition to radiation induced sarcoma: possible role for BRCA and p53 mutations.
abstract: The estimated incidence of radiation-associated sarcoma (RAS) is 0.03-0.2 % in 5 years post treatment. Most cancer predisposing genes are involved in DNA repair; therefore, elevated RAS risk in these patients is plausible. Cases of angiosarcoma post breast cancer treatment were reported in BRCA1 and BRCA2 carriers. We report the genetic evaluation of seven cases with suspected RAS from patients counseled in our cancer-genetic clinic. Of 2,885 breast cancer patient, 470 were BRCA1 or two mutation carriers and three were p53 mutation carriers. Of them seven developed sarcoma in the field of irradiation; five in the chest wall and two in other sites. Genetic evaluation revealed BRCA1 mutation in two, BRCA2 mutation in additional patient and a carrier of p53 mutation. The estimation of risk for RAS in patients with genetic predisposition is limited due to the rarity of this event, and the bias in referral to the clinic toward younger age. With these limitations the rate of RAS is 0.43 % (2/470, 95 % CI -0.17 to 1.02, SE = 0.3) in this group in a median follow-up of 8.2 years (range 1 month to 51 years). If we assume irradiation for the breast in 80 % of the patients than rate of RAS in group is proximately 0.53 % (2/376, 95 % CI -0.21 to 1.26, SE = 0.37). A BRCA1 carrier which had sarcoma after irradiation to head and neck carcinoma was not included in these analyses. In conclusion, we found a high frequency of BRCA1/2 mutation among our patients diagnosed with RAS. However, we estimated approximately twofold increase in the risk of RAS in BRCA1/2 carriers which was not significant compared to reports in general population. Therefore, RAS is a rare event in BRCA carriers as in the general population, and should not be considered in the decision regarding irradiation treatment in this population.
authors.affiliation: Sharett Institute of Oncology, Hadassah Medical Center, Hebrew University, Jerusalem, Israel. luna@hadassah.org.il
authors.forename: Luna
authors.initials: L
authors.lastname: Kadouri
authors.forename: Michal
authors.initials: M
authors.lastname: Sagi
authors.forename: Yael
authors.initials: Y
authors.lastname: Goldberg
authors.forename: Israela
authors.initials: I
authors.lastname: Lerer
authors.forename: Tamar
authors.initials: T
authors.lastname: Hamburger
authors.forename: Tamar
authors.initials: T
authors.lastname: Peretz
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects*; D012509:Sarcoma / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human